(a) Field
The present invention relates to apparatus, systems and methods for performing in situ measurements, and, more particularly, to apparatus, systems and methods that can isolate a sample from a bulk fluid to measure characteristics of same without unwanted effects of perturbation in the bulk fluid.
(b) Description of the Related Art
In situ measurement and the use of probes in implementing the same are subjects of much current interest due to their tremendous variety of applications. Whether it be for the monitoring of a cell culture, aquatic systems, or ecosystems, the accurate measurement of parameters in the system is useful for detecting natural, spatial, and/or temporal variations.
This type of undertaking is ideally performed in situ as the conventional approach of sample removal from the system, storage, and/or transport heightens the risk for contamination and inaccurate measurement of system conditions. In bioreactor processes, for instance, the ability to monitor cellular physiological states and system parameters is essential to control and maintain the system at desired conditions.
In the cell culture context, the tracking of metabolic states is very important for, e.g. designing feeding strategies, process scale-up, and calculation of optimal harvest time, etc. A commonly used indicator of metabolic activity in cells is the oxygen uptake rate or OUR.
One conventional method of measuring OUR, known as the dynamic method, requires stopping all gas supply then monitoring the oxygen consumption over time. This creates a harsh and significant disturbance to the cells, which consequently impacts cell proliferation, results in potentially erroneous readings, and does not allow for an extended period of continuous, real-time monitoring.
Another conventional method, illustrated in FIG. 1A, involves drawing a sample from the bioreactor and transferring it to an external vessel equipped with a monitoring and control system. Conditions, such as pH, temperature, aeration, etc., in the external vessel must be adjusted and controlled to mirror those of the bioreactor in order to obtain accurate and reliable readings. Duplicating these conditions, however, is challenging and time-consuming. In light of the above, apparatus and methods for in situ measurements that reduce the effects of system perturbations are highly desirable.